EAGER/Collaborative Research: Experimentally Validated Modeling of the Dynamics of Carbon Dioxide Removal from the Bloodstream via Peritoneal Perfluorocarbon Circulation

这个早期概念探索性研究（EAGER）项目汇集了一个由控制工程师、生物医学工程师、医学研究人员和临床医生组成的多学科团队，探索一种新的不依赖肺部的方法来补充动物的气体交换。具体来说，研究小组将研究含氧全氟碳（PFC）通过大型动物的腹部（腹膜腔）的循环是否可以作为清除动物血液中二氧化碳（CO2）的途径；以及二氧化碳清除过程的控制动力是什么。在这种情况下，腹膜腔基本上充当“第三肺”，为肺功能受损超过机械通气可达到的支持的患者提供关键的生命支持。在COVID-19大流行的背景下，目前迫切需要这种治疗，但该系统也有可能成为数十万肺衰竭患者重症监护的标准模式。此外，医学界将受益于对腹膜氧合PFC循环去除二氧化碳能力的深刻理解，这将是将该技术引入未来临床试验的基本要素。该项目解决了建立一个实验验证的模型的挑战，即二氧化碳从大型动物的血液输送到经动物腹腔（腹膜）灌注的含氧全氟碳化合物的动力学。利用作为该项目的一部分获得的实验数据，该团队将开发并参数化控制二氧化碳去除的运输动力学的面向控制的多室模型。虽然之前的腹膜含氧PFC循环实验主要检查准稳定条件，但研究团队将通过精心设计基础实验来确保其数据的丰富性，以最大限度地提高二氧化碳去除动力学的可识别性。结果将是一个比准稳定数据集更适合于底层系统动力学建模和估计的数据集。系统动力学和控制社区将受益于将其科学工具和方法应用于新型通风技术的动态建模的机会。特别重要的是，这种建模可以帮助将动态系统和控制学科的跨学科影响扩大到新的健康相关应用技术的程度。紧急而严格地应对这一研究挑战，有可能为医学研究界提供关键援助，特别是考虑到COVID-19危机。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This EArly-concept Grant for Exploratory Research (EAGER) project brings together a multidisciplinary team of control engineers, biomedical engineers, medical researchers, and clinicians to explore a novel pulmonary-independent method for supplementing gas exchange in an animal. Specifically, the research team will study whether the circulation of oxygenated perfluorocarbon (PFC) through the abdomen (the peritoneal cavity) of a large animal, can serve as a pathway for clearing carbon dioxide (CO2) from the animal’s bloodstream; and what are the governing dynamics of this CO2 clearing process. The peritoneal cavity essentially acts as a “third lung” in this scenario, providing critical life support for patients whose compromised lung function has exceeded the support achievable through mechanical ventilation. There is currently a critical need for this treatment, within the context of the COVID-19 pandemic, but this system also has potential to emerge as a standard modality in the critical care of hundreds of thousands of patients in pulmonary failure. Furthermore, the medical community will benefit from the deep fundamental understanding of the CO2 removal capabilities of peritoneal oxygenated PFC circulation, which will be an essential element in bringing this technology into future clinical trials.This project addresses the challenge of building an experimentally validated model of the dynamics of carbon dioxide transport from the bloodstream of a large animal into oxygenated perfluorocarbon perfused through the animal’s abdominal (peritoneal) cavity. Using the experimental data obtained as part of this project, the team will develop and parameterize a control-oriented, multi-compartment model of the transport dynamics governing CO2 removal. While previous experiments on peritoneal oxygenated PFC circulation have predominantly examined quasi-steady conditions, the research team will ensure the richness of its data by deliberately designing the underlying experiments to maximize the identifiability of the CO2 removal dynamics. The result will be a dataset better suited for the modeling and estimation of underlying system dynamics than the quasi-steady datasets. The system dynamics and control community will benefit from the opportunity to apply its scientific tools and methods to the dynamic modeling of a novel ventilation technology. Particularly important is the degree to which such modeling can help broaden the interdisciplinary impact of the dynamic systems and controls discipline to a new health-related application technology. Addressing this research challenge urgently, but rigorously, has the potential to provide critical assistance to the medical research community, particularly considering the COVID-19 crisis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.